Identification of three antiviral inhibitors against Japanese encephalitis virus from library of pharmacologically active compounds 1280

PLoS One. 2013 Nov 4;8(11):e78425. doi: 10.1371/journal.pone.0078425. eCollection 2013.

Abstract

Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate. There is no antiviral drug available for JEV-specific treatment. In this study, a cytopathic-effect-based, high-throughput screening assay was developed and applied to screen JEV inhibitors from Library of Pharmacologically Active Compounds 1280. The antiviral effects of three hit compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in cells by western blotting, indirect immunofluorescence assay, and plaque reduction assay. A time-of-addition assay proved that all three compounds inhibited JEV at the stage of replication. The EC50s of FGIN-1-27, cilnidipine, and niclosamide were 3.21, 6.52, and 5.80 µM, respectively, while the selectivity indexes were 38.79, 30.67, and 7.49. FGIN-1-27 and cilnidipine have high efficiency and selectivity against JEV. This study provided two JEV antiviral inhibitors as candidates for treatment of JEV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Blotting, Western
  • Dihydropyridines / pharmacology
  • Encephalitis Virus, Japanese / drug effects*
  • Fluorescent Antibody Technique
  • Indoleacetic Acids / pharmacology
  • Niclosamide / pharmacology

Substances

  • Antiviral Agents
  • Dihydropyridines
  • Indoleacetic Acids
  • N,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide
  • Niclosamide
  • cilnidipine

Grants and funding

This work was supported by the 973 Project (2010CB530100), National Natural Science Foundation (30800831), 863 Program (2011AA10A212), National Special Research Programs for Non-Profit Trades (201203082), Fundamental Research Funds for the Central University (2013JC001) and innovative research groups of NSFC (31121004) in from China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.